Combinatorial synthesis and biomarker development

Abstract

Provided herein are methods, kits, and compositions for use in the diagnosis and treatment of diseases. Peptoids recognized by Alzheimer's disease specific antibodies are identified.

1 - 109 . (canceled) 
     
     
         110 . A method comprising:
 a. contacting a sample with a non-random peptoid library, wherein said non-random peptoid library comprises one or more peptoid or pharmaceutically acceptable salt thereof having an affinity to an antibody; and   b. detecting whether said antibody is bound to said one or more peptoid or pharmaceutically acceptable salt thereof.   
     
     
         111 . The method of  claim 110 , wherein said antibody is bound to said one or more peptoid or pharmaceutically acceptable salt thereof. 
     
     
         112 . The method of  claim 111 , wherein said antibody comprises an IgA or a fragment thereof. 
     
     
         113 . The method of  claim 111 , wherein said antibody comprises an IgM or a fragment thereof. 
     
     
         114 . The method of  claim 111 , wherein said detecting comprise identifying a binding between said one or more peptoid or pharmaceutically acceptable salt thereof and at least two antibody isotypes. 
     
     
         115 . The method of  claim 114 , wherein said at least two antibody isotypes comprises at least one of an IgG, IgM, IgD, IgE or an IgA. 
     
     
         116 . The method of  claim 111 , wherein the detecting utilizes a method comprising radio immunoassay (“RIA”), fluorescence immunoassay (“FIA”), enzyme-linked immunosorbent assay (“ELISA”), western blot, flow cytometry, Forster resonance energy transfer (“FRET”), surface plasmon resonance, or any combination thereof. 
     
     
         117 . The method of  claim 110 , wherein said sample is tissue, cell, urine, serum, whole blood, cerebrospinal fluid, sputum, saliva, or semen. 
     
     
         118 . The method of  claim 117 , wherein said sample is serum. 
     
     
         119 . The method of  claim 110 , wherein said sample is from a subject suspected of having a disease. 
     
     
         120 . The method of  claim 119 , wherein said disease is a neurological disease. 
     
     
         121 . The method of  claim 120 , wherein said neurological disease is Parkinson's disease. 
     
     
         122 . The method of  claim 120 , wherein said neurological disease is Alzheimer's disease. 
     
     
         123 . The method of  claim 110 , wherein said one or more peptoid or pharmaceutically acceptable salt thereof has a binding affinity of at least 10 −5  M (K D ) for said antibody. 
     
     
         124 . The method of  claim 110 , wherein said one or more peptoid or pharmaceutically acceptable salt thereof is associated with a support. 
     
     
         125 . The method of  claim 124 , wherein there is a linker between said support and said one or more peptoid or pharmaceutically acceptable salt thereof. 
     
     
         126 . The method of  claim 125 , wherein said linker comprises a polyethylene glycol (“PEG”) linker. 
     
     
         127 . The method of  claim 124 , wherein said solid support is a glass slide, silicon surface, bead, resin or an array. 
     
     
         128 . The method of  claim 124 , wherein said solid support is associated with a brush polymer. 
     
     
         129 . The method of claim124, wherein said solid support is associated with a bottle brush polymer. 
     
     
         130 . The method of claim110, further comprising repeating (a) and (b) at different time points to monitor a disease. 
     
     
         131 . The method of  claim 110 , wherein said one or more peptoid or pharmaceutically acceptable salt thereof comprises a formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is independently selected from a group consisting of a coupling group capable of coupling to a linker, a substrate, or a label; hydrogen; deuterium; C 1-6  alkyl; C 2-6  alkenyl; C 2-6  alkynyl, C 3-8 cycloalkyl; heteroaryl, cycloalkyl; C 1-6 alkylheteroaryl; C 1-6 alkylaryl; and alkylcycloalkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 2  is independently selected from a group consisting of hydrogen; deuterium; (CY 2 ) n -aryl; (CY 2 ) n -alkoxyaryl; cycloalkyl; (CY 2 ) n -heteroaryl; and (CY 2 ) n -alkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 3  is independently selected from a group consisting of (CY 2 ) n -aryl; (CY 2 ) n -alkoxyaryl; alkenyl; alkylaryl; cycloalkyl; alkyldiaryl; and alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 4  is independently selected from a group consisting of (CY 2 ) n -aryl; alkyl; cycloalkyl; and (CY 2 ) n -alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 5  is independently selected from a group consisting of (CY 2 ) n -aryl; (CY 2 ) n -alkyl; alkyl; and alkyldiaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 6  is independently selected from a group consisting of alkyldiaryl; alkylaryl; and (CY 2 ) n -alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 7  is independently selected from a group consisting of alkyl; alkylaryl; (CY 2 ) n -aryl; (CY 2 ) n -alkyl; and alkyldiaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 8  is independently selected from a group consisting of (CY 2 ) n -heteroaryl; (CY 2 ) n -aryl; alkenyl; (CY 2 ) n -alkyl; alkyl; and alkyldiaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 9  is independently selected from a group consisting of alkylaryl; (CY 2 ) n -aryl; alkyldiaryl; and (CY 2 ) n -alkyl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 10  is independently selected from a group consisting of (CY 2 ) n -aryl; alkyl; (CY 2 ) n -alkyl; and (CY 2 ) n -heteroaryl; each of which may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 11  is independently selected from a group consisting of hydrogen; deuterium; C 1-6  alkyl; C 2-6  alkenyl; C 2-6  alkynyl, C 3-8 cycloalkyl; heteroaryl, cycloalkyl; C 1-6 alkylheteroaryl; C 1-6 alkylaryl; and alkylcycloalkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 12  is independently selected from a group consisting of a coupling group capable of coupling to a linker, a substrate, or a label; hydrogen; deuterium; C 1-6  alkyl; C 2-6  alkenyl; C 2-6  alkynyl, C 3-8 cycloalkyl; heteroaryl, cycloalkyl; C 1-6 alkylheteroaryl; C 1-6 alkylaryl; and alkylcycloalkyl; each of which except hydrogen and deuterium may be individually and independently substituted one or more times with XA; halogen; NY 2 ; CXXY; XCY 3 ; alkyl; hydrogen; deuterium; carboxylic acid; ether; amine; XX 2 NY 2 ; ═X; XCY 2 X or any combinations thereof; 
         R 13  is individually and independently selected from a group consisting of hydrogen; deuterium; a halogen; ethyl; and methyl; wherein when R 13  is not hydrogen each carbon denoted with an * can independent be R or S; wherein X is independently selected from oxygen or sulfur; Y is independently selected from deuterium or hydrogen; A is hydrogen, deuterium, aryl, or heteroaryl and n is 1-10.